Changes in endomorphin-2-like immunoreactivity in inflammatory and nerve injury conditions
Description
Inflammation and nerve injury often lead to chronic, sometimes excruciating pain. The mechanisms contributing to this syndrome include neurochemical plasticity in neurons involved in the earliest stages of pain transmission. Endomorphin-2 (Tyr-Pro-Phe-Phe-NH2, EM2) is an endogenous morphine-like substance that binds to the mu-opioid receptor with high affinity and selectivity. EM2-like immunoreactivity (EM2-LI) is present in the superficial layers of the dorsal horn in the spinal cord and in primary afferents, suggesting a role for this peptide in pain transmission Immunocytochemical studies revealed that unilateral sciatic nerve ligation (Seltzer model) produced dramatic reductions in EM2-LI and substance P-LI (SP-LI) ipsilateral to the injury from 4--14 days after injury in mice. Calcitonin gene-related peptide-LI (CGRP-LI) remained unchanged throughout the study. Control animals did not show any side-to-side changes. The neuropeptide changes were accompanied by significant thermal hyperalgesia. In rats, a novel triple-ligature nerve injury model was sufficient to produce significant reductions in EM2-LI and SP-LI ipsilateral to the injury from 4--14 days after injury. Dynorphin-LI (DYN-LI) was significantly increased during this time. As with the mouse model, CGRP-LI was unchanged. The neuropetide alterations in this study were concurrent with both thermal hyperalgesia and thermal and mechanical allodynia In contrast to nerve injury, a unilateral inflammatory stimulus (CFA) failed to produce significant changes in SP-LI or EM2-LI at 2h, 24h, 3d or 7d after intraplantar injection of CFA in rats. These results are consistent with other studies which suggest that opioids may not be altered after inflammation The decrease in EM2-LI during the development of chronic pain is consistent with a loss of an inhibitory influence on pain transmission. The results provide the first evidence that reduction of an endogenous opioid in primary afferents is associated with injury-induced chronic pain